This work is designed to elucidate controls of catch-up (compensatory) growth and proportionate growth and also to determine whether proportionate growth has priority over growth in individual dimensions. The studies will employ rat models in which growth is disturbed by X-irradiation of the head during the neonatal period, or, after weaning, by fasting, cortisone injections, or propylthiouracil feeding. In order to determine whether brain mechanisms are involved in the control of catch-up and of proportionate growth X-irradiation of the head will be employed in combination with each of the other experimental treatments. Measurements of body size, organ weight, tibial length, and skeletal age will be used to assess growth. The results will be correlated with measurements of growth hormone and somatomedin in serum and of cartilage uptake of sulfate, in vivo and in vitro, and in vivo only of leucine, thymidine, uridine, and proline. The pattern of pulsatile secretion of growth hormone will be investigated in these experimental models in order to explain the increased levels of plasma growth hormone we have previously found during recovery fasted, cortisone- and propylthiouracil-treated rats. If abnormalities of pulsatile secretion occur, running activity cycles in blinded rats submitted to these experimental treatments will be studied in order to determine whether the 24-hour clock is also disturbed by the treatment. Studies of energy expenditure by spontaneous running activity and of nitrogen losses in urine and feces will be carried out in order to investigate further the cause of the energy inefficiency for growth and maintenance which we have previously found in coincidence with failure of catch-up growth after cortisone treatments of rats. Studies will be continued on purification and identification and determination of the biological significance of a factor in normal rat serum which was found to inhibit thymidine uptake by cartilage in vitro.